NIH – FDA COVID SIG Lecture: Viral RNA Sensors in Human Immunity to SARS-CoV-2

This is an NIH – FDA COVID-19 SIG seminar talk. Helen Su, M.D., Ph.D., is chief of the Human Immunological Diseases Section in NIAID. LECTURE SUMMARY: Impaired type I IFN responses can lead to life-threatening COVID-19. Previous reports have established that the endosomal viral RNA sensors TLR3 and TLR7 initiate protective type I IFN responses during SARS-CoV-2 infections in humans. However, the role of the cytosolic RIG-I-like receptors (RLRs), which are more broadly expressed, has been less well studied. We investigated rare variants in the genes encoding MDA5, RIG-I, and their downstream signaling adaptor MAVS,from a large international cohort of SARS-CoV-2-infected subjects with varying disease severities. By identifying andfunctionally characterizing these variants, as well as testing patients ’ blood and fibroblasts, we have delineated cross-regulatory positive amplification loops by which RLRs non-redundantly promote type I IFN responses in humans. Thus, human variation in viral sensors can influence outcome to COVID-19 and possibly other respiratory viruses. LECTURE OBJECTIVES: (1) To understand the role of viral RNA sensors in initiatingand sustaining antiviral type I IFN responses; (2) To appreciate how human genetic variation can modulate immune responses during viral infections.Air date: 6/29/2023 12:00:00 PM
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